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Nat Microbiol. 2016 Jun 6;1(8):16082. doi: 10.1038/nmicrobiol.2016.82.

Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer.

Author information

1
Institute for Research in Biomedicine, University of Italian Switzerland, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
2
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
3
Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland.
4
Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
5
Laboratori Sperimentali di Ricerca-Area Trapiantologica, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
6
Institute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
7
Istituto Nazionale Genetica Molecolare 'Romeo ed Enrica Invernizzi', 20122 Milano, Italy.

Abstract

Human cytomegalovirus encodes at least 25 membrane glycoproteins that are found in the viral envelope(1). While gB represents the fusion protein, two glycoprotein complexes control the tropism of the virus: the gHgLgO trimer is involved in the infection of fibroblasts, and the gHgLpUL128L pentamer is required for infection of endothelial, epithelial and myeloid cells(2-5). Two reports suggested that gB binds to ErbB1 and PDGFRα (refs 6,7); however, these results do not explain the tropism of the virus and were recently challenged(8,9). Here, we provide a 19 Å reconstruction for the gHgLgO trimer and show that it binds with high affinity through the gO subunit to PDGFRα, which is expressed on fibroblasts but not on epithelial cells. We also provide evidence that the trimer is essential for viral entry in both fibroblasts and epithelial cells. Furthermore, we identify the pentamer, which is essential for infection of epithelial cells, as a trigger for the ErbB pathway. These findings help explain the broad tropism of human cytomegalovirus and indicate that PDGFRα and the viral gO subunit could be targeted by novel anti-viral therapies.

PMID:
27573107
PMCID:
PMC4918640
DOI:
10.1038/nmicrobiol.2016.82
[Indexed for MEDLINE]
Free PMC Article

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